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Open Access 01-09-2015 | Original Article

Cancer treatment-related neuropathic pain: proof of concept study with menthol—a TRPM8 agonist

Authors: M. T. Fallon, D. J. Storey, A. Krishan, C. J. Weir, R. Mitchell, S. M. Fleetwood-Walker, A. C. Scott, L. A. Colvin

Published in: Supportive Care in Cancer | Issue 9/2015

Abstract

Purpose

Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol.

Patients and methods

Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation.

Results

Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed.

Conclusion

This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required.

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Title: Cancer treatment-related neuropathic pain: proof of concept study with menthol—a TRPM8 agonist
Authors: M. T. Fallon
D. J. Storey
A. Krishan
C. J. Weir
R. Mitchell
S. M. Fleetwood-Walker
A. C. Scott
L. A. Colvin
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: Supportive Care in Cancer / Issue 9/2015
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-015-2642-8

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